Noninvasive methods and systems of determining the extent of tissue capture from cardiac pacing

ABSTRACT

Methods and systems of evaluating cardiac pacing in candidate patients for cardiac resynchronization therapy and cardiac resynchronization therapy patients are disclosed. The methods and systems disclosed allow treatments to be personalized to patients by measuring the extent of tissue capture from cardiac pacing under various therapy parameter conditions. Systems and methods of optimizing right ventricle only cardiac pacing are also disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is related to commonly owned U.S. patent applicationSer. No. ______ (Attorney Docket No. C00013060.USU2), titled “METHODSAND SYSTEMS OF OPTIMIZING RIGHT VENTRICULAR ONLY PACING FOR PATIENTSWITH RESPECT TO AN ATRIAL EVENT AND LEFT VENTRICULAR EVENT” filed on thesame day herewith, which is incorporated herein by reference in itsentirety.

In addition, this application claims the benefit of U.S. ProvisionalApplication No. 62/300,675, filed on Feb. 26, 2016. The disclosure ofthe above application is incorporated herein by reference in itsentirety.

BACKGROUND

Doctors and other medical professionals may evaluate performancecharacteristics of the heart to provide individualized treatment topatients using cardiac resynchronization therapy. The beat of the heartis controlled by the sinoatrial node (SA node), a group of conductivecells located in the right atrium near the entrance of the superior venacava. A depolarization signal generated by the SA node activates theatrioventricular node (AV node). The AV node briefly delays thepropagation of the depolarization signal, allowing blood in the atria todrain into the ventricles, before passing the depolarization signal tothe ventricles of the heart. The coordinated contraction of bothventricles drives the flow of blood through the torso of a patient. Incertain circumstances, the conduction of the depolarization signal fromthe AV node to the left and right ventricles may be interrupted orslowed. This may result in a dyssynchrony in the contraction of the leftand right ventricles, and eventually in heart failure or death.

Cardiac Resynchronization Therapy (CRT) may correct the symptoms ofelectrical dyssynchrony by providing pacing therapy to one or bothventricles or atria, e.g., by providing pacing to encourage earlieractivation of the left or right ventricles. By pacing the contraction ofthe ventricles, the ventricles may be controlled so that the ventriclescontract in synchrony. Some patients undergoing CRT have experiencedimproved ejection fraction, increased exercise capacity, and an improvedfeeling of well-being.

Providing CRT to a patient may involve determining whether the patientwill derive benefit from the CRT prior to implantation of a cardiacrhythm device. Additionally, detailed evaluations may aid in determiningoptimal placement of one or more ventricular pacing leads or optimalprogramming of device parameters, such as selection of electrodes onmulti-polar right or left ventricular leads, as well as selection of thetiming of the pacing pulses delivered to the electrodes, such asatrioventricular (A-V) and intra-ventricular (V-V) delays.

SUMMARY

Methods and systems of evaluating cardiac pacing in candidate patientsfor cardiac resynchronization therapy and cardiac resynchronizationtherapy patients are disclosed.

In one aspect, the present disclosure provides a method of determiningthe extent of applied cardiac tissue stimulation due to pacing. Themethod includes applying electrodes on a patient's torso, pacing thepatient's cardiac tissue, receiving torso-surface potential signalsdetected by the electrodes, determining an activation time for eachelectrode, determining the number of electrodes that register anactivation time that meets predetermined criteria, calculating apercentage index by dividing the number of electrodes that registered anactivation time that meets a predetermined criteria by the total numberof electrodes distributed on the patient's torso, determining the extentof applied cardiac tissue stimulation due to pacing based on thepercentage index.

In one or more embodiments, the method includes pacing the cardiactissue to avoid interference with the intrinsic rhythm of the heart.Further, the predetermined criteria may be a predetermined activationtime threshold. The predetermined criteria may be a predetermined timeperiod within which the activation time of electrodes must beregistered. For example, the predetermined time period may be about 5ms, 10 ms, 15 ms, or 20 milliseconds from a specified time origin wherethe specified time origin is the earliest activation time detected for acorresponding depolarization cycle. The predetermined time period mayalso be a percentile of the activation-times registered by theelectrodes.

In one or more embodiments, the method may include adjusting atherapeutic parameter value based on the extent of applied cardiactissue electrical stimulation due to pacing. The therapeutic parametermay include the magnitude of the energy applied by the pacing source.Additionally, the therapeutic parameter may be the direction of a pacingvector applied by the pacing source. The direction of the pacing vectormay be determined from the geometry of the device.

In one or more embodiments, the system to determine the extent ofapplied cardiac tissue stimulation due to pacing includes electrodesconfigured to be distributed on a patent's torso, a pacing deviceconfigured to stimulate the patent's cardiac tissue, a processing unitconfigured to determine the number of electrodes that register anactivation time that meet as predetermined criteria, calculate apercentage index by dividing the number of electrodes that registeredactivation times that meet the predetermined criteria by the totalnumber of electrodes distributed on the patient's torso and determinethe extent of applied cardiac tissue stimulation due to pacing based onthe percentage index.

In one or more embodiments, the distributed electrodes include at least20 electrodes. Additionally, in one or more embodiments, the pacingdevice is implanted in the patient and comprises a lead in directcontact with cardiac tissue. The pacing device may include a processingunit. The pacing device may also include two electrodes located on thesame lead. The pacing device may communicate wirelessly with theprocessing unit.

In one or more embodiments, the pacing device may be an external devicefor applying pacing using an ultrasound wave.

In one or more embodiments, the method of determining the extent ofapplied cardiac tissue stimulation due to pacing may include applyingstimulation to the patient's cardiac tissue and receiving potentialsignals detected at a first time period, determining the extent ofapplied cardiac tissue stimulation due to pacing based on activationtimes derived from the potential signals received at the first timeperiod, adjusting a therapeutic parameter related to the delivery of thestimulation to the patient's cardiac tissue based on the determinedextent of applied cardiac tissue electrical stimulation due to pacing,in order to meet a predetermined treatment goal applying stimulation tothe patient's cardiac tissue and receiving potential signals detected ata second time period determining the extent of applied cardiac tissuestimulation due to pacing based on the potential signals received at thesecond time period, determining if the adjustment of the therapeuticparameter resulted in meeting the predetermined treatment goal.

In one or more embodiments, the therapeutic parameter may be themagnitude of the energy applied by the pacing source. In one or moreembodiments, the therapeutic parameter is the direction of a pacingvector applied by the pacing source. The direction of the pacing vectormay be determined from the geometry of a pacing device. Additionally, inone or more embodiments, the therapeutic parameter may be a timinginterval between successive stimulations of the cardiac tissue.

In one or more embodiments, the predetermined treatment goal may includeincreasing the extent of applied cardiac tissue stimulation due topacing within a predetermined time period. In one or more embodiments,the predetermined treatment goal may include decreasing the extent ofapplied cardiac tissue stimulation due to pacing within a predeterminedtime period.

In one or more embodiments, a system to determine the extent of appliedcardiac tissue stimulation due to pacing may include electrodesconfigured to be distributed on a patent's torso, a means forstimulating the patent's cardiac tissue, a means for determining thenumber of electrodes that register an activation time that meet aspredetermined criteria, a means for calculating a percentage index bydividing the number of electrodes that registered activation times thatmeet the predetermined criteria by the total number of electrodesdistributed on the patient's torso, and a means for determining theextent of applied cardiac tissue stimulation due to pacing based on thepercentage index.

In one or more embodiments, the means for stimulating the patent'scardiac tissue is implanted in the patient. In one or more embodiments,the means for stimulating the patent's cardiac tissue is external to thepatient's body. In one or more embodiments, the means for determiningthe extent of applied cardiac tissue stimulation due to pacing isimplanted in the patient. In one or more embodiments, the means fordetermining the extent of applied cardiac tissue stimulation due topacing is external to the patient's body.

In one or more embodiment, a method of determining the extent of appliedcardiac tissue stimulation due to pacing includes applying electrodes ona patient's torso, pacing the patient's cardiac tissue, the pacing ofthe cardiac tissue is timed to avoid interference with the intrinsicrhythm of the heart, receiving torso-surface potential signals detectedby the electrodes, determining an activation time for each electrode,determining the number of electrodes that register an activation timethat meets a predetermined criteria, calculating a percentage index bydividing the number of electrodes that registered an activation timethat meets the predetermined criteria, the predetermined criteriacomprises a predetermined time period within which the activation timeof electrodes must be registered, by the total number of electrodesdistributed on the patient's torso, determining the extent of appliedcardiac tissue stimulation due to pacing based on the percentage index.

The present disclosures will aid in assessing the effectiveness ofvarious treatment method, devices, and parameters by allowing healthcare provides to non-invasively asses the amount of cardiac tissuecapture during treatment. Further, non-invasive methods or techniques ofstimulating cardiac tissue in combination with the methods and systemsdisclosed herein will enable patient's cardiac functions to be analyzedwithout the need for invasive surgery.

BRIEF DESCRIPTION OF THE DRAWINGS/FIGURES

FIG. 1 is a conceptual diagram illustrating an example system that maybe used to provide CRT to a heart of a patient.

FIG. 2 is a timing diagram showing an example ECG tracing of two healthyheart beats.

FIG. 3 is a timing diagram showing an example ECG tracing of a patientsuffering from left bundle branch block.

FIGS. 4A and 4B are conceptual diagrams illustrating example systems formeasuring torso-surface potentials.

FIG. 5 is a block diagram illustrating an example system for measuringtorso-surface potentials.

FIG. 6 is a series of simulated isochrone maps of torso-surfaceactivation times for typical left bundle branch block intrinsic rhythmand CRT pacing.

FIG. 7 is a flow diagram illustrating an example operation of a systemto provide indications of the cardiac electrical dyssynchrony of apatient based on torso-surface activation times.

FIG. 8 is a flow diagram illustrating an example technique forprescribing and configuring CRT based on an assessment cardiacelectrical dyssynchrony of a patient via the torso-surface activationtimes.

FIG. 9 is a series of isochrone maps of cardiac activation timesconstructed with two different heart-torso models using body-surface ECGdata from the same patient.

FIG. 10 is a flow diagram illustrating an example operation of a systemto measure the cardiac electrical dyssynchrony of a patient via thecardiac activation times.

FIG. 11 is a flow diagram illustrating an example technique forconfiguring CRT based on an assessment of cardiac electricaldyssynchrony of a patient via the cardiac activation times.

FIG. 12 is a flow diagram illustrating a technique for determiningwhether a patient is a good candidate for right ventricle only pacingaccording to some embodiments of the present invention.

FIG. 13 is a flow diagram illustrating a technique for determining theoptimal right ventricle pacing delay percentage according to someembodiments of the present invention.

FIG. 14 is a flow diagram illustrating a technique of adaptivelyapplying right ventricular only cardiac pacing according to someembodiments of the present invention.

FIG. 15 is a flow diagram illustrating a technique for determining theextent of applied cardiac stimulation according to some embodiments ofthe present invention.

FIG. 16 is a set of graphical representations showing global electricalheterogeneity and resynchronization values of a heart determined usingan ECG Belt according to some embodiments of the present invention.

DETAILED DESCRIPTION

The present disclosure is directed to methods and systems for evaluatingthe performance of a heart using a multi-electrode electrocardiogram(ECG). Additionally, the present disclosure is directed to methods andsystems of optimizing right ventricular only cardiac pacing.

Assessment of electrical dyssynchrony for these purposes has typicallyinvolved assessing QRS duration clinically. Though CRT is typicallyrecommended for patients with wide QRS duration, hemodynamicimprovements through CRT have been reported in narrow QRS heart failurepatients. Thus, some patients who may benefit from CRT may not beprescribed CRT based on present electrical dyssynchrony evaluationtechniques. The methods and systems disclosed herein are directed totechniques for evaluating electrical dyssynchrony in the heart of apatient, the amount of activation of heart tissue in response to pacing,and methods and systems to optimize CRT therapy.

Evaluating the performance of the heart requires particular systems formapping heart performance characteristics. For example, a set ofelectrodes may be spatially distributed about the torso of a patient.The electrodes may each sense a body surface potential signal, and moreparticularly a torso-surface potential signal, which indicates thedepolarization signals of the heart of the patient after the signalshave progressed through the torso of the patient. Due to the spatialdistribution of the electrodes, the torso-surface potential signalrecorded by each electrode may indicate the depolarization of adifferent spatial region of the heart. Additionally, the strength orother signal characteristics may be recorded.

In some examples, an activation time is determined for eachtorso-surface potential signal, i.e., for each electrode of the set. Thedispersion or sequence of these activation times may be analyzed orpresented to provide a variety of indications of the electricaldyssynchrony of the heart of the patient. For example, isochrone orother activation maps of the torso-surface illustrating the activationtimes may be presented to a doctor or other medical professional toillustrate electrical dyssynchrony of the heart. In some examples,values of one or more statistical indices indicative of the temporaland/or spatial distribution of the activation times may be determined.Such maps and indices, or other indications of dyssynchrony determinedbased on the torso-surface activation times, may indicate electricaldyssynchrony of the heart to a user, and facilitate evaluation of apatient for CRT, and configuration of CRT for the patient. In someembodiments of the present invention, the extent of applied cardiacstimulation in response to CRT may be evaluated by comparing the numberof activating torso-surface electrodes to the total number oftorso-surface electrodes. The extent of applied cardiac stimulation in aspecific section of the heart may be determined. That is, the extent ofapplied cardiac stimulation in a specific area of the heart, forexample, the left ventricle, may be determined using similar methods.

In some examples, the locations of all or a subset of the electrodes,and thus the locations at which the torso-surface potential signals aresensed, may be projected on the surface of a model torso that includes amodel heart. The inverse problem of electrocardiography may be solved todetermine electrical activation times for regions of the model heartbased on the torso-surface potential signals sensed from the patient. Inthis manner, the electrical activity of the heart of the patient may beestimated. Various isochrone or other activation time maps of thesurface of the model heart may be generated based on the torso-surfacepotential signals sensed on the surface of the torso of the patient.Further, values of one or more indices indicative of the temporal and/orspatial distribution of the activation times on model heart may bedetermined. These measures and representations of electricaldyssynchrony may be used to evaluate the suitability of the patient forCRT, adjust the positioning of the CRT leads during implantation, ordetermine which electrodes of one or more multi-polar leads should beutilized for delivery of CRT, as well as the timing of pacing pulses,such as atrioventricular (A-V) and intra-ventricular (V-V) delays fordelivery of CRT to the patient.

For example, the one or more indications of dyssynchrony may bedetermined or generated based on data collected both during intrinsicconduction and during CRT. The degree of dyssynchrony during intrinsicconduction and CRT may be compared, e.g., to determine whether a patientis a candidate for CRT. Similarly, the one or more indications ofdyssynchrony may be determined or generated based on data collectedduring CRT with different lead positions, different electrodeconfigurations, and/or different CRT parameters, e.g., A-V or V-V delay.The change in dyssynchrony attributable to these different leadpositions, different electrode configurations, and/or different CRTparameters may be evaluated.

Some patients receiving CRT have right heart conduction delays. Rightheart conduction delays may be caused by right bundle branch blocks orby non-specific interventricular conduction disorders. Right heartconduction delays result in a dyssynchrony in the ventricles of theheart. The dyssynchrony may cause additional stress on the heart and maylead to heart failure and death. When the dyssynchrony and theconduction delay is only in the right ventricle but not in the leftventricle, the condition may be potentially ameliorated by pacing theright ventricle at appropriate timing to achieve synchronization withconduction in the left heart which leads to reduction in globalelectrical heterogeneity during ventricular depolarization (QRS). Globalelectrical heterogeneity may be quantified by measures of dispersion ofelectrical activation times over the entire heart which may includestatistical measures like mean, variance, standard deviation, range orinter-quartile deviation applied to activation times which may bemeasured by noninvasive body-surface mapping techniques. The disclosureherein is also directed to pacing the right ventricle in response to anatrial signal at an atrioventricular (AV) delay time determined as apercentage of the delay between the atrial signal and the left ventricleactivation. Methods and systems of optimizing the atrioventricular delaytime for right ventricular signal only pacing are also disclosed.

The details of one or more aspects of the disclosure are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages will be apparent from the description anddrawings, and from the claims.

The effectiveness of CRT depends on many factors including thepositioning of the CRT leads during implantation, the use of one or moremulti-polar leads the timing of pacing pulses, such as atrioventricular(A-V) and intra-ventricular (V-V) delays for delivery of CRT to thepatient. Various systems and devices can be used for sensing bioelectricdata from a human body. For example, multi-electrode electrocardiogram(ECG) systems can be utilized for body-surface potential mapping byrecording simultaneous ECG measurements from multiple sensors orelectrodes applied to selected locations of a patient's body. Thesesensors may be included in apparatus such as vests, bands, belts,straps, patches, wearable garments, t-shirts, bras, hats (e.g., forneural signals), etc.

Some ECG systems include multiple sensors generally arranged as part ofa vest that is attached to a patient. These vests can be applied to apatient's torso for receiving bioelectric signals and, in someconfigurations, delivering stimulating signals to the patient.Bioelectric signals from the patient are detected by the sensors andtransmitted via conductive paths to a medical monitoring system orapparatus such as an ECG base unit.

For example, one type of electrode vest is described in U.S. Pat. No.6,055,448 to Anderson et al., entitled SENSOR DEVICE. The describeddevice includes a plurality of finger-like substrate portions of aflexible dielectric material that are releasably attachable to thethoracic region of a human body.

Further, for example, U.S. Patent Publication No. 2013/0018251 to Caprioet al., entitled SENSOR DEVICE WITH FLEXIBLE JOINTS, describes a sensordevice that includes a flexible dielectric substrate, a plurality ofsensors distributed on the substrate, and an electrically conductivenetwork distributed on the substrate connecting the sensors to aterminal portion of the substrate. Integrated flexible joints permit acertain amount of elasticity in and allow relative movement between atleast two of the sensors when the sensor device is placed onto the humanbody.

Such vests are generally provided in multiple sizes to accommodatevarious body types and sizes of patients. For example, U.S. PatentPublication No. 2011/0190615 to Phillips et al., entitled ELECTRODEPATCH MONITORING DEVICE, describes an electrode patch monitoring devicethat includes an array of electrodes formed on a flexible substrate. Theelectrode patch monitoring device may be available in a plurality ofsizes.

U.S. Pat. No. 8,972,228 to Subham et al., entitled ASSESSINGINTRA-CARDIAC ACTIVATION PATTERNS, incorporated herein in its entiretyby reference, describes a sensor system and techniques that useelectrodes to determine the characteristics of the heart when the heartis stimulated. The techniques described aid in evaluating cardiacelectrical dyssynchrony.

Further U.S. Patent Application No. 62/152,684 entitled METHOD FOREFFICIENT DELIVERY OF MULTI-SITE PACING, incorporated herein in itsentirety by reference, describes systems, methods, apparatuses, andtechniques relating to the delivering of electrical stimulation to theheart.

FIG. 1 is a conceptual diagram illustrating an example system that maybe used to provide CRT to heart 10 of patient 1. The system may includean implantable medical device (IMD) 100. IMD 100 may be a CRT pacemakeror CRT defibrillator. IMD 100 may be equipped with one or more leads;leads 102, 104, and 106; that are inserted into or on the surface of theleft ventricle 12, right ventricle 14, or right atrium 16 of heart 10.Leads 102, 104, and 106 may be equipped with one or more electrodes 108,110, and 112.

Heart 10 may suffer from an electrical dyssynchrony. Electricaldyssynchrony may occur when the depolarization signals that start thecontraction of ventricles 12 and 14 do not reach the ventricles in acoordinated manner, which results in an inefficient pumping action ofheart 10. Patient 1 may experience symptoms of heart failure. Electricaldyssynchrony may be caused by damage to the electrical system of heart10, e.g., a bundle branch block or damage to the fascicle of heart 10.Alternate conduction pathways may form within heart 10, but thesepathways may slow the progress of the electrical depolarization signaland result in the asynchronous contraction of ventricles 12 and 14.

IMD 100 may provide CRT stimulation to heart 10 of patient 1. IMD 100 isdepicted as being configured to deliver stimulation to right atrium 16,right ventricle 14, and left ventricle 12 of heart 10. In otherexamples, IMD 100 may be configured to deliver stimulation to otherportions of heart 10 depending on the condition of patient 1. IMD 100may interact with an external programmer (not shown) to adjust operatingcharacteristics, such as A-V and V-V delays, of the therapy delivered byIMD 100. In some examples, IMD 100 may also be configured to sense theelectrical activity of heart 10 through the electrodes on one or more ofleads 102, 104, and 106.

As shown in FIG. 1, leads 102, 104, 106 may extend into the heart 10 ofpatient 1 to deliver electrical stimulation to heart 10 and synchronizethe contraction of ventricles 12 and 14. Right ventricular lead 106extends through one or more veins (not shown), the superior vena cava(not shown), and right atrium 16, and into right ventricle 14. Leftventricular coronary sinus lead 102 extends through one or more veins,the vena cava, right atrium 16, and into the coronary sinus (not shown)to a region adjacent to the free wall of left ventricle 12 of heart 10.Right atrial lead 104 extends through one or more veins and the venacava, and into the right atrium 16 of heart 10.

In other configurations, IMD 100 may be equipped with more or fewerleads, depending on the requirements of the therapy provided to patient1. For example, IMD 100 may be equipped with leads that extend togreater or fewer chambers of heart 10. In some example, IMD 100 may beequipped with multiple leads that extend to a common chamber of heart,e.g., multiple leads extending to the left ventricle 12. IMD 100 mayalso be equipped with one or more leads that are placed on the heartthrough other means providing access to the cardiac tissue, such assurgical epicardial lead placement, and other pericardial accessapproaches. In some examples, IMD 100 may be equipped with a leftventricular lead that is placed on the heart endocardially.Additionally, although illustrated as implanted on the right side ofpatient 1 in FIG. 1, IMD 100 may in other examples be implanted on theleft side of the pectoral region of the patient, or within the abdomenof the patient.

Electrodes 108, 110, and 112 may attach to portions of heart 10 toprovide electrical stimulation or sense the electrical depolarizationand repolarization signals of heart 10. Electrode 108, in rightventricle 14, may be affixed to the wall of heart 10 via a screw basedmechanism. Electrode 110 may comprise multiple electrodes mounted thesame lead, allowing lead 102 to both transmit therapeutic shocks as wellas electrical sense data detected by electrode 110. Electrodes 110 and112 may be attached to the surface of heart 10 via adhesive, barbs, oranother permanent or semi-permanent attachment mechanism. Additionally,the heart tissue may be stimulated using other stimulation techniques.For example, an ultrasonic or acoustic wave may be targeted at aspecific region of the heart to promulgate a depolarization signal. Anexample of a configuration in which ultrasonic pacing is delivered tocardiac tissue over the skin may be seen with respect to U.S. patentapplication Ser. No. 15/009,817 filed Jan. 28, 2016, and assigned to theassignee of the present invention, the disclosure of which isincorporated by reference in its entirety herein.

FIG. 2 is a timing diagram showing an example ECG tracing 200 inconjunction with certain periods or phases of the mechanical cardiaccycle. The depiction and associated description of FIG. 2 aregeneralized in the sense that the relationship between the timing ofelectrical and mechanical events is not necessarily as described for allsubjects, or at all times for any given subject.

ECG tracing 200 depicts the electrical signal of two example healthycardiac cycles. The electrical signal of a healthy heart comprises aseries of 5 characteristic waves: the P-wave, Q-wave, R-wave, S-wave,and T-wave. Each of these waves, and the intervals between them,correspond to discrete events in the functioning of a healthy heart.

In general, at some point during period 202, which stretches from thepeak of a P-wave to the peak of the subsequent R-wave, atrial systoleoccurs, which is the contraction of the atria that drives blood from theatria into the ventricles. Period 204, from the peak of the R-wave tothe opening of the aortic valve, generally marks a period ofisovolumetric contraction. The atrioventricular and aortic valves areclosed, preventing blood flow and leading to an increase in pressure inthe ventricles but not yet in the aorta. Period 206, bounded by theopening and closing of the aortic valves is generally when ejectionoccurs during the cardiac cycle. During ejection period 206 theventricles contract and empty of blood, driving the blood intocardiovascular system. As the contraction of the ventricles complete,the pressure of the blood within the cardiovascular system closes theaortic valves. Period 208, bounded by the closing of the aortic valvesand the opening of the atrioventricular valves, is the isovolumetricrelaxation of the ventricles. Periods 210 and 212 are collectively knownas the late diastole, where the whole heart relaxes and the atria fillwith blood. Period 210 corresponds to a rapid inflow of blood whileperiod 212 corresponds to diastasis, the period of slower flow bloodinto the atria before the atrial systole 202 occurs again.

The P-wave marks the stimulation of the atria and the beginning of thecardiac cycle. The atria contract under the stimulation, forcing bloodinto the ventricles. The PR segment marks the delay as thedepolarization signal travels from the atrioventricular node to thePurkinje fibers. The Q-wave marks the depolarization of theinterventricular septum as an initial part of the depolarization of theventricles. The R-wave follows the Q-wave and represents thedepolarization of the ventricles. The S-wave follows the R-wave andrepresents the later depolarization of the ventricles. The T-wave marksthe recovery and repolarization of the ventricles in preparation for thenext beat of the heart.

The QRS complex, spanning from the beginning of the Q-wave to the end ofthe S-wave, represents the electrical activation of the myocardium.Ventricular contraction of both the left and right ventricles is inresponse to the electrical activation. The QRS complex typically lastsfrom 80 to 120 ms. The relatively large amplitude of the QRS complex isdue to the large muscle mass of the ventricles. Issues affecting thesynchrony of the ventricular contraction may be demonstrated in thedeformation of the QRS complex. For example, electrical dyssynchrony inthe contraction of the ventricles can widen the R-wave or produce twoR-wave peaks, typically labeled the r-wave and R′-wave, corresponding tothe depolarization of each ventricle. The S-wave and the T-wave may bemorphologically different than in an ECG tracing of a healthy heart.

FIG. 3 is a timing diagram showing ECG tracing 300. ECG tracing 300depicts the electrical signal of a patient suffering from a left bundlebranch block. A sign of the condition is the presence of an rS complexversus the typical QRS complex, though other variations of Q, R, and Swaves form combinations that may be present in patients suffering from aleft bundle branch block, right bundle branch blocks, or otherventricular conduction conditions. The extended duration of the rScomplex indicates an extended ventricular contraction time, likely dueto electrical dyssynchronies.

Diagnosis of a left or right bundle branch block, or cardiac electricaldyssynchrony in general, typically involves measuring the duration ofthe QRS complex (or other complex marking the depolarization of theventricles). QRS complexes lasting 100 ms or longer may indicate apartial bundle branch block and 120 ms or longer a complete bundlebranch block. In FIG. 3, the initial Q-wave is not visible, instead thetracing shows an initial r-wave, corresponding to the initialdepolarization of the right ventricle and followed by an S-wave markingthe rapid depolarization of both ventricles after the cardiac signal hasreached the left ventricle after traveling through the myocardium of theheart, rather than through the bundle branches. Because the myocardiumconducts electricity more slowly than the bundle branches, the entirecomplex is spread out over a longer period.

Absent a case of bundle branch block—such as the one shown in FIG. 3—orother condition, diagnosis may be more challenging. Thus, occultdyssynchronies may be present that, while responsive to CRT, may not bereadily identifiable from an examination of the typical 12-lead ECG.These occult dyssynchronies may manifest in the electrical signalsgenerated by the heart and measured on the surface of the torso and maybe diagnosable through alternative means of analysis, such as bydetermining cardiac activation times at a plurality of spatiallydistributed locations according to the techniques described herein.

FIGS. 4A and 4B are conceptual diagrams illustrating example systems formeasuring body-surface potentials and, more particularly, torso-surfacepotentials. In one example illustrated in FIG. 4A, sensing device 400A,comprising a set of electrodes 404A-F (generically “electrodes 404”) andstrap 408, is wrapped around the torso of patient 1 such that theelectrodes surround heart 10. As illustrated in FIG. 4A, electrodes 404may be positioned around the circumference of patient 1, including theposterior, lateral, and anterior surfaces of the torso of patient 1. Inother examples, electrodes 404 may be positioned on any one or more ofthe posterior, lateral, and anterior surfaces of the torso. Electrodes404 may be electrically connected to processing unit 500 via wiredconnection 406. Some configurations may use a wireless connection totransmit the signals sensed by electrodes 404 to processing unit 500,e.g., as channels of data.

Although in the example of FIG. 4A sensing device 400A comprises strap408, in other examples any of a variety of mechanisms, e.g., tape oradhesives, may be employed to aid in the spacing and placement ofelectrodes 404. In some examples, strap 408 may comprise an elasticband, strip of tape, or cloth. In some examples, electrodes 404 may beplaced individually on the torso of patient 1.

Electrodes 404 may surround heart 10 of patient 1 and record theelectrical signals associated with the depolarization and repolarizationof heart 10 after the signals have propagated through the torso ofpatient 1. Each of electrodes 404 may be used in a unipolarconfiguration to sense the torso-surface potentials that reflect thecardiac signals. Processing unit 500 may also be coupled to a return orindifferent electrode (not shown) which may be used in combination witheach of electrodes 404 for unipolar sensing. In some examples, there maybe 12 to 16 electrodes 404 spatially distributed around the torso ofpatient 1. In other examples, there may be more than 40 electrodes 404distributed around the torso of patient 1. Other configurations may havemore or fewer electrodes 404.

Processing unit 500 may record and analyze the torso-surface potentialsignals sensed by electrodes 404. As described herein, processing unit500 may be configured to provide an output to a user indicating theelectrical dyssynchrony in heart 10 of patient 1. The user may make adiagnosis, prescribe CRT, position therapy devices, e.g., leads, oradjust or select treatment parameters based on the indicated electricaldyssynchrony.

In some examples, the analysis of the torso-surface potential signals byprocessing unit 500 may take into consideration the location ofelectrodes 404 on the surface of the torso of patient 1. In suchexamples, processing unit 500 may be communicatively coupled to animaging system 501, which may provide an image that allows processingunit 500 to determine coordinate locations of each of electrodes 404 onthe surface of patient 1. Electrodes 404 may be visible, or madetransparent through the inclusion or removal of certain materials orelements, in the image provided by imaging system 501.

FIG. 4B illustrates an example configuration of a system that may beused to evaluate electrical dyssynchrony in heart 10 of patient 1. Thesystem comprises a sensing device 400B, which may comprise vest 410 andelectrodes 404 A-ZZ (generically “electrodes 404”), a processing unit500, and imaging system 501. Processing unit 500 and imaging system 501may perform substantially as described above with respect to FIG. 4A. Asillustrated in FIG. 4B, electrodes 404 are distributed over the torso ofpatient 1, including the anterior, lateral, and posterior surfaces ofthe torso of patient 1.

Sensing device 400B may comprise a fabric vest 410 with electrodes 404attached to the fabric. Sensing device 400B may maintain the positionand spacing of electrodes 404 on the torso of patient 1. Sensing device400B may be marked to assist in determining the location of electrodes404 on the surface of the torso of patient 1. In some examples, theremay be 150 to 256 electrodes 404 distributed around the torso of patient1 using sensing device 400B, though other configurations may have moreor fewer electrodes 404.

FIG. 5 is a block diagram illustrating an example system for measuringtorso-surface potentials and providing indications of electricaldyssynchrony. The example system may comprise a processing unit 500 anda set of electrodes 404 on a sensing device 400, e.g., one of examplesensing devices 400A or 400B (FIGS. 4A and 4B). The system may alsoinclude an imaging system 501.

As illustrated in FIG. 5, processing unit 500 may comprise a processor502, signal processor 504, memory 506, display 508, and user inputdevice 509. Processing unit 500 may also include an electrode locationregistration module 524.

In the illustrated example, processor 502 comprises a number of modulesand, more particularly, a projection module 514, an inverse problemmodule 516, an activation time module 518, an indices module 520, and anisochrones mapping module 522. Memory 506 may store recorded data 510and models 512.

Processing unit 500 may comprise one or more computing devices, whichmay be co-located, or dispersed at various locations. The variousmodules of processing unit 500, e.g., processor 502, projection module514, inverse problem module 516, activation time module 518, statisticsmodule 520, isochrones mapping module 522, signal processor 504,electrode location registration module 524, display 508, memory 506,recorded data 510 and torso models 512 may be implemented in one or morecomputing devices, which may be co-located, or dispersed at variouslocations. Processor 502, and the modules of processor 502, may beimplemented in one or more processors, e.g., microprocessors, of one ormore computing devices, as software modules executed by theprocessor(s). Electrode location registration module 524 may, in someexamples, be implemented in imaging system 501.

In addition to the various data described herein, memory 506 maycomprise program instructions that, when executed by a programmableprocessor, e.g., processor 502, cause the processor and any componentsthereof to provide the functionality attributed to a processor andprocessing unit herein. Memory 506 may include any volatile,non-volatile, magnetic, optical, or electrical media, such as a harddisk, magnetic tape, random access memory (RAM), read-only memory (ROM),CD-ROM, non-volatile RAM (NVRAM), electrically-erasable programmable ROM(EEPROM), flash memory, or any other digital or analog media. Memory 506may comprise one or more co-located or distributed memories. Memory 506may comprise a tangible article that acts as a non-transitory storagemedium for data and program instructions.

The torso-surface potential signals sensed by electrodes 404 of sensingdevice 400 may be received by signal processor 504 of processing unit500. Signal processor 504 may include an analog-to-digital converter todigitize the torso-surface potential signals. Signal processor 504 mayalso include various other components to filter or otherwise conditionthe digital signals for receipt by processor 502.

Electrode location registration module 524 may receive imaging data fromimaging system 501. Electrode location registration module 524 analyzesthe imaging data. In particular, electrode registration location module524 identifies electrodes 404, or elements co-located with theelectrodes that are more clearly visible via the imaging modality,within the images. Electrode location registration module 524 mayfurther identify the locations of each of the electrodes on the surfaceof the patient and/or within a three-dimensional coordinate system. Insome examples, the locations of electrodes 404 may be manuallyidentified and registered with processing unit 500, e.g., by a user, viaelectrode registration module 524.

The imaging data may comprise data representing one or more images ofpatient 1 wearing electrodes 404, e.g., of a sensing device 400. In someexamples, the images may be obtained before or during a medicalprocedure, e.g., a surgical procedure to implant a cardiac rhythm deviceand lead system for delivery of CRT.

In some examples, processor 502 may store the torso-surface potentialsignals, imaging data from imaging system, electrode location data fromelectrode location registration module, or any values disclosed hereinthat are derived by processing of such signals and data by processor502, within memory 506 as recorded data 510. Each recorded torso-surfacepotential signal, or other values derived therefrom, may be associatedwith a location of the electrode 404 that sensed the torso-surfacepotential signal. In this manner, the torso-surface potential data maybe correlated with the position of electrodes 404 on the torso ofpatient 1, or within a three-dimensional coordinate system, enablingspatial mapping of the data to particular locations on the surface ofthe torso or within the coordinate system. In some examples, aspects ofthe techniques described herein may be performed at some time after theacquisition of the torso-surface potential signals and location databased on recorded data 510.

Processor 502 may be configured to provide one or more indications ofelectrical dyssynchrony based on the torso-surface potential signalsand, in some examples, the electrode location data. Example indicationsof electrical dyssynchrony include indices illustrating activation timesfor each electrode/location distributed about the torso or heart, or forone or more subsets of electrodes located within a common region, e.g.,within a left posterior, left anterior, right posterior, or rightanterior region. In some examples, processor 502 may be configured toprovide a set of two or more different indications, e.g., severaldifferent indications, for each of two or more different regions, e.g.,several different regions, of the torso or heart.

Some indications of dyssynchrony may include statistical values or otherindices derived from activation times for each electrode location or oneor more subsets of electrodes within one or more regions. Other examplesindications of electrical dyssynchrony that may be determined based onactivation times at various electrodes/locations include graphicalindications, such as an isochrone or other activation maps, or ananimation of electrical activation. Other examples indications ofelectrical dyssynchrony that may be determined based on activation timesat various electrodes/locations include identifying one of apredetermined number of dyssynchrony levels, e.g., high, medium, or low,via text or color, e.g., red, yellow, green, for example.

In some examples, the various indications of dyssynchrony for one ormore regions may be determined based on data collected at two or moredifferent times and/or under two or more different conditions. Forexample, the various indications of dyssynchrony may be determined basedon torso-potential signals collected during intrinsic conduction ofheart 10, and also determined based on torso-potential signals collectedduring CRT. In this manner, the potential dyssynchrony-reducing benefitof CRT may be evaluated for the patient by comparing the differentvalues, graphical representations, or the like, resulting from intrinsicconduction and CRT. A short pacing signal reduces the potential forinterference from the intrinsic or natural pacing of the heart. Asanother example, the various indications of dyssynchrony may bedetermined each of a plurality of different times based ontorso-potential signals collected during delivery of CRT with differentlead positions, electrode configurations, or CRT parameters, e.g., A-Vor V-V interval values. In this manner, the relativedyssynchrony-reducing benefits of the different lead positions,electrode configurations, or CRT parameters positions may be evaluatedfor the patient by comparing the different values, graphicalrepresentations, or the like.

Models 512 may include a plurality of different models, e.g.,three-dimensional models, of the human torso and heart. A model torso ormodel heart may be constructed by manual or semi-automatic imagesegmentation from available databases of previously acquired medicalimages (CT/MRI) of a plurality of subjects, e.g., cardiomyopathypatients, different than patient 1, using commercially availablesoftware. Each model may be discretized using a boundary element method.A plurality of different torso models may be generated. The differentmodels may represent different subject characteristics, such asdifferent genders, disease states, physical characteristics (e.g., largeframe, medium frame and small frame), and heart sizes (e.g., x-large,large, medium, small). By providing input via user input 509, a user mayselect from among the various model torsos and model hearts that may bestored as models 512 in memory 506, so that the user may more closelymatch the actual torso and heart 10 of patient 1 with the dimensions andgeometry of a model torso and model heart. In some examples, medicalimages of the patient, e.g., CT or MRI images, may be manually orsemi-automatically segmented, registered, and compared to models 512 forselection from amongst the models 512. Furthermore, single or multipleview 2-D medical images (e.g., x-ray, fluoroscopy) may be segmented ormeasured to determine approximate heart and torso dimensions specific tothe patient in order to select the best fit model torso and heart.

Projection module 514 may project the locations of electrodes 404, e.g.,stored as recorded data 510 within of memory 506, onto an appropriate,e.g., user-selected, model torso contained in model data module 512 ofmemory 506. By projecting the location of electrodes 404 onto the modeltorso, projection module 514 may also project the torso-surfacepotential signals of patient 1 sensed by electrodes 404 onto the modeltorso. In other examples, the measured electrical potentials may beinterpolated and resampled at electrode positions given by the model. Insome examples, projecting the torso-surface potentials onto the modeltorso may allow processor 502, via inverse problem module 516, toestimate the electrical activity of at various locations or regions ofthe model heart corresponding to heart 10 of patient 1 that produced themeasured torso-surface potentials.

Inverse problem module 516 may be configured to solve the inverseproblem of electrocardiography based on the projection of the measuredtorso-surface potentials, recorded by electrodes 404, onto the modeltorso. Solving the inverse problem of electrocardiography may involvethe estimation of potentials or activation times in heart 10 based on arelationship between the torso and heart potentials. In one examplemethod, model epicardial potentials are computed from model torsopotentials assuming a source-less volume conductor between the modelheart and the model torso in an inverse Cauchy problem for Laplace'sequation. In another example method, an analytic relationship betweentorso-surface potentials and the cardiac transmembrane potential isassumed. Torso-surface potentials may be simulated based on thisrelationship. In some examples, inverse problem module 516 may utilizetechniques described by Ghosh et al. in “Accuracy of Quadratic VersusLinear Interpolation in Non-Invasive Electrocardiographic Imaging(ECGI),” Annals of Biomedical Engineering, Vol. 33, No. 9, September2005, or in “Application of the L1-Norm Regularization to EpicardialPotential Solution of the Inverse Electrocardiography Problem,” Annalsof Biomedical Engineering, Vol. 37, No. 5, 2009, both of which areincorporated herein by reference in their entireties. In other examples,any known techniques for solving the inverse problem ofelectrocardiography may be employed by inverse problem module 516.

Activation time module 518 may compute the activation times directlyfrom measured torso-surface potentials, or by estimating modeltransmembrane potentials. In either case, an activation time for eachelectrode/location may be determined as a time period between twoevents, such as between the QRS complex onset and the minimum derivative(or steepest negative slope) of the sensed torso potential signal orestimate epicardial potential signal. Thus, in one example, cardiacactivation times are estimated from the steepest negative slope of themodel epicardial electrograms. Cardiac activation times (parameters inthe analytic relationship between torso-surface potential and cardiactransmembrane potential) may, in other configurations, be computed basedon minimizing the least square difference between the measuredtorso-surface potentials and simulated torso-surface potentials. Acolor-coded isochrone map of ventricular, epicardial, or torso-surfaceactivation times may be shown by display 308. In other examples, display308 may show a two-color animation of propagation of the activationwavefront across the surface of the model heart or the torso-surface.

Indices module 520 may be configured to compute one or more indices ofelectrical dyssynchrony from the torso-surface or cardiac activationtimes. These indices may aid in the determination of whether the patientis a candidate for CRT, placement of CRT leads, and selection of CRTparameters. For example, LV lead 102 (FIG. 1) may be positioned at thesite that reduces dyssynchrony from one or more indices or,alternatively, the largest electrical resynchronization as demonstratedby the indices. The same indices may be also used for programming A-Vand/or V-V delays during follow-up. As indicated above, the indices maybe determined based on the activation times for allelectrodes/locations, or for one or more subsets of electrodes in one ormore regions, e.g., to facilitate comparison or isolation of a region,such as the posterior and/or left anterior, or left ventricular region.

One of the indices of electrical dyssynchrony may be a standarddeviation index computed as the standard deviation of theactivations-times (SDAT) of some or all of electrodes 404 on the surfaceof the torso of patient 1. In some examples, the SDAT may be calculatedusing the estimated cardiac activation times over the surface of a modelheart.

A second example index of electrical dyssynchrony is a range ofactivation times (RAT) which may be computed as the difference betweenthe maximum and the minimum torso-surface or cardiac activation times,e.g., overall, or for a region. The RAT reflects the span of activationtimes while the SDAT gives an estimate of the dispersion of theactivation times from a mean. The SDAT also provides an estimate of theheterogeneity of the activation times, because if activation times arespatially heterogeneous, the individual activation times will be furtheraway from the mean activation time, indicating that one or more regionsof heart 10 have been delayed in activation. In some examples, the RATmay be calculated using the estimated cardiac activation times over thesurface of a model heart.

A third example index of electrical dyssynchrony estimates thepercentage of electrodes 404 located within a particular region ofinterest for the torso or heart, whose associated activation times aregreater than a certain percentile, for example the 70th percentile, ofmeasured QRS complex duration or the determined activation times forelectrodes 404. The region of interest may be a posterior, leftanterior, and/or left-ventricular region, as examples. This index, thepercentage of late activation (PLAT), provides an estimate of percentageof the region of interest, e.g., posterior and left-anterior areaassociated with the left ventricular area of heart 10, which activateslate. A large value for PLAT may imply delayed activation of substantialportion of the region, e.g., the left ventricle 12 (FIG. 1), and thepotential benefit of electrical resynchronization through CRT bypre-exciting the late region, e.g., of left ventricle 12. In otherexamples, the PLAT may be determined for other subsets of electrodes inother regions, such as a right anterior region to evaluate delayedactivation in the right ventricle. Furthermore, in some examples, thePLAT may be calculated using the estimated cardiac activation times overthe surface of a model heart for either the whole heart or for aparticular region, e.g., left or right ventricle, of the heart.

Isochrone mapping module 522 may be configured to generate an isochronemap depicting the dispersion of activation times over the surface of thetorso of patient 1 or a model heart. Isochrone mapping module 522 mayincorporate changes in the torso-surface or cardiac activation times innear real-time, which may permit near instant feedback as a user adjustsa CRT device or monitors patient 1 to determine if CRT is appropriate.Isochrone maps generated by isochrone mapping module 522 may bepresented to the user via display 508.

In general, processor 502 may generate a variety of images or signalsfor display to a user via display 508 based on the measuredtorso-surface potentials, calculated torso-surface or estimated cardiacactivation times, or the degree of change in electrical dyssynchrony.For example, a graded response reflecting the efficacy of a particularlocation of the LV lead 102 during biventricular pacing or singleventricle fusion pacing may be provided to the physician in terms of ared, yellow and green signal. A red signal may be shown if the reductionin electrical dyssynchrony during CRT pacing compared to intrinsicrhythm is negative (an increase in electrical dyssynchrony) or minimal,e.g., less than 5%. A yellow signal may be triggered if there is somereduction in electrical dyssynchrony during CRT pacing compared tointrinsic rhythm, for example between 5% and 15%, but there may bepotentially better sites for lead placement. If the reduction inelectrical dyssynchrony during CRT pacing compared to intrinsic rhythmis substantial, e.g., greater than 15%, a green signal may be triggeredindicating to the physician that the present site provides effectivechanges in synchronization. The feedback from this system in combinationwith other criteria (like magnitude of pacing threshold, impedance,battery life, phrenic nerve stimulation) may be also used to choose anoptimal pacing vector for one or more multipolar leads. The feedbackfrom this system may be also used for selecting optimal device timings(A-V delay, V-V delay, etc) influencing the extent of fusion ofintrinsic activation with paced activation from single or multipleventricular sites, or discerning acute benefit of single site fusionpacing versus multi-site pacing and choice of appropriate pacing type.

Display 508 may also display three-dimensional maps of electricalactivity over the surface of the torso of patient 1 or over a modelheart. These maps may be isochrone maps showing regions of synchronouselectrical activity as the depolarization progresses through heart 10 ofpatient 1. Such information may be useful to a practitioner indiagnosing asynchronous electrical activity and developing anappropriate treatment, as well as evaluating the effectiveness of thetreatment.

FIG. 6 is a series of simulated isochrone maps 600 of torso-surfaceactivation times over the torso of a patient suffering from anelectrical dyssynchrony in the left ventricle before and duringtreatment with a CRT device. The isochrone maps before (intrinsic) andafter treatment are divided into two views: anterior and posterior. Line602 represents the location of a subset of electrodes 404, e.g., asubset of electrodes 404 of sensing device 400B, that may be used tocalculate one or more indices of electrical dyssynchrony. In someexamples, line 602 may represent electrodes 404 on sensing device 400A.

The isochrone maps 600 of the natural and CRT assisted torso-surfaceactivation times may be generated using multiple electrodes 404distributed over the surface of the torso of a patient, e.g., usingsensing device 400B. Generation of the isochrone maps 600 may includedetermining the location of electrodes 404, and sensing torso-surfacepotential signals with the electrodes. Generation of the isochrone maps600 may further include calculating the torso-surface activation timefor each electrode or electrode location by determining the point in therecorded QRS complex of the signal sensed by the electrodescorresponding to the maximum negative slope. In other examples, thetorso-surface activation times may be determined by identifying theminimum derivative of the QRS complex. The measured torso-surfaceactivation times may then be standardized and an isochrone map of thesurface of the torso of the patient generated.

The delayed activation of certain locations associated with certain onesof electrodes 404 due to the electrical dyssynchrony is apparent in theposterior views of the intrinsic torso-surface activation times. Regions604 indicate increased delay in the activation of the underlying heart.The corresponding posterior view during treatment with a CRT deviceindicate that regions 606, the same location as regions 604 on the mapsof intrinsic torso-surface activation times, exhibits increasedsynchrony in electrical ventricular activity. The CRT maps exhibitdecreased range and a lower standard deviation of torso-surfaceactivation times. Further, the posterior regions no longer exhibitdelayed activation times. The isochrone map of the torso-surfaceactivation times during intrinsic and CRT pacing and changes indistribution of activation-times from intrinsic to CRT pacing may beused for diagnostic purposes or the adjustment of a CRT device.

One or more indices of electrical dyssynchrony may also be calculatedfrom the torso-surface activation times used to generate isochrone maps600. For example, SDAT, an indication of the spread of the activationtimes, for the patient's intrinsic heart rhythm using the complete setof electrodes 404 is 64. Using the reduced lead set marked by line 602results in an SDAT of 62. The RAT for the intrinsic heart rhythm andcomplete lead set is 166.5 while the reduced lead set has a RAT of 160.PLAT for the intrinsic heart rhythm using the reduced and complete leadsets are 56.15% and 66.67%, respectively. This indicates that using areduced lead set that circumscribes the heart of the patient, e.g.,sensing device 400A and associated electrodes 404, may providecomparable indices of electrical dyssynchrony compared to using anelectrode set covering the torso of the patient, such as sensing device400B.

The indices of electrical dyssynchrony also provide indication of theeffectiveness of the CRT device, with the SDAT for the reduced set ofelectrodes declining to 24, the RAT to 70 and PLAT to 36%. Thisindicates that the torso-surface activation times during CRT treatmentwere more narrowly distributed and in a smaller range than in the normalheart rhythm and that the percentage of electrodes 404 located on theleft anterior surface of the torso of the patient registering lateactivation times decreased markedly.

FIG. 7 is a flow diagram illustrating an example operation of a systemto evaluate the cardiac electrical dyssynchrony of a patient via thetorso-surface activation times. The location of electrodes, e.g.,electrodes 404 (FIGS. 4A and 4B), distributed over the surface of thetorso of the patient may be determined (700). A cardiac event, e.g., adepolarization, may generate an electrical signal that propagatesthrough the torso of a patient, e.g., patient 1 (FIG. 1) and registerson the electrodes. The signal sensed by the electrodes may be received(702), e.g., by processing unit 500 (FIG. 5). The processing unit maycalculate the torso-surface activation times (704). In some examples,the processing unit may also construct a torso-surface activation timesisochrone map (706). The processing unit may also calculate at least oneindex of cardiac electrical dyssynchrony (708). These indices maycomprise one or more of the SDAT (710), RAT (712), and the PLAT (714).

A cardiac event, such as a depolarization, generates an electricalsignal that propagates through the torso. The electrical signal maycomprise a QRS complex, or a variant caused by a heart related conditionsuch as a left or right bundle branch block. The electrical signal maynot propagate uniformly through the torso of a patient due to variationsin conductivity within the torso and the heart. These delays maymanifest in electrodes distributed over the surface of the torso of thepatient registering the same electrical signal at different points intime.

The electrical signal generated by the cardiac event may register on theplurality of electrodes distributed over the surface of the torso ofpatient. The electrodes may be distributed over the anterior, lateral,and/or posterior surfaces of the torso, allowing the generation of athree-dimensional picture of the electrical activity occurring withinthe torso. In some examples, the electrodes may be placed to provideextensive coverage both above and below the heart, e.g., by usingsensing device 400B (FIG. 4B). In other examples, a reduced set ofelectrodes may be arranged around the circumference of the torso,circumscribing the heart of the patient, e.g., using sensing device 400A(FIG. 4A). The electrodes may receive the complete waveform of theelectrical signal generated by the cardiac event, and transmit thesignal to a processing unit.

The location of electrodes distributed over the surface of the torso ofthe patient may be determined (700). Locating the electrodes may beperformed automatically, e.g. by imaging system 501 and electrodelocation registration module 524 of processing unit 500 (FIG. 5). Theelectrodes may be located by analyzing one or more images of the torsoof a patient and performing a pattern matching routine, e.g.,recognizing the shape of an electrode against the torso of the patient,and storing the location of the electrode on the torso of the patient inprocessing unit memory. In other examples, the location of sensingdevice 400A or 400B may be determined and the locations of theelectrodes determined based on the position of the sensing device, e.g.,basing the position of the electrode on the patient through the knownposition of the electrode on the sensing device. In another example, theposition of the electrodes may be measured manually.

The processing unit may receive the electrical signal from theelectrodes and record the output in memory (702). The processing unitmay record the raw output, e.g., the raw ECG tracing from eachelectrode, as well as location data for the electrodes, allowing theelectrical signals detected by the electrodes to be mapped onto thesurface of the torso of the patient.

The processing unit may compute the torso-surface activation times(704). A processor, e.g., processor 502 of processing unit 500 (FIG. 5),may retrieve ECG tracing data stored within the processing unit memoryand analyze the tracing to detect depolarization of the ventricles ofthe heart, typically marked by a QRS complex in the tracing. Theprocessor may, in some examples, detect ventricular depolarization bydetermining the time of the minimum derivative (or steepest negativeslope) within the QRS complex measured with respect to the time of QRScomplex onset. The determination of the activation time may be made foreach electrode and stored in the processing unit memory.

In some configurations, the processing unit may construct an isochronemap of the torso-surface activation times, allowing the user to visuallyinspect the propagation of the electrical signals of the heart afterprogression through the torso of the patient. The isochrone map may beconstructed by dividing the range of measured torso-surface activationtimes into a series of sub-ranges. The location of each electrode on thesurface of the torso of the patient may be graphically represented.Regions of electrodes whose measured activation times fall within thesame sub-range may be represented by the same color on the graphicalrepresentation.

The processing unit may also calculate one or more indices of electricaldyssynchrony based on the torso-surface activation times (708). Theseindices may include the SDAT (710), RAT (712), and PLAT (714). In someexamples, the PLAT may be determined as the percentage of posteriorelectrodes activating after a certain percentage of the QRS complexduration.

As discussed above, in some examples, the construction of atorso-surface activation times isochrone map (706), or other graphicalrepresentation of dyssynchrony, as well as the calculation of indices ofelectrical dyssynchrony (708), may be performed for a particular regionof the torso based the signals received from electrodes (702) in suchregions. Graphical representations and indices of electricaldyssynchrony may be determined for each of a plurality of regions basedon the signals received from the electrodes for such regions. In someexamples, the representations and indices for various regions may bepresented together or compared.

FIG. 8 is a flow diagram illustrating an example technique for measuringthe cardiac electrical dyssynchrony of a patient via measuredtorso-surface activation times. A processing unit 500 may receivetorso-surface potential signals from a plurality of electrodes (800),e.g., electrodes 404 (FIGS. 4A and 4B). The processing unit 500 maycalculate the torso-surface activation times for each of the pluralityof electrodes (802). The processing unit 500 may provide at least oneindication of cardiac electrical dyssynchrony (804).

A user may evaluate the whether a patient is a candidate for CRT basedon the at least one indication of electrical dyssynchrony (806). Theuser may also monitor the at least one indication of electricaldyssynchrony (808), and use the changes in the at least one indicationto aid in adjusting the positioning of electrodes, e.g., electrodes 108,110, and 112 (FIG. 1), during implantation of a CRT device (810), e.g.,IMD 100 (FIG. 1), or selection of the various programmable parameters,such as electrode combination and the A-V or V-V pacing intervals, ofthe CRT device (812), during implantation or a follow-up visit.

The various indications of cardiac electrical dyssynchrony describedherein, such as statistical or other indices, or graphicalrepresentations of activation times, may indicate the presence of damageto electrical conductivity of the heart of the patient, for example thepresence of a left or right bundle branch block, that may not beapparent from the examination of a standard 12-lead ECG readout. Forexample, a large SDAT indicates that the activation of the ventricles isoccurring over a large time span, indicating that the depolarization ofthe ventricles is not occurring simultaneously. A large RAT alsoindicates a broad range of activation times and asynchronous contractionof the ventricles. A high PLAT indicates that a specific region of theheart, e.g., the posterior regions associated with the left ventricle,may be failing to activate in concert with the measured QRS complex.Additionally, by monitoring the at least one indication of cardiacelectrical dyssynchrony, the user may detect changes in the electricalactivity of the heart caused by different treatments or treatmentconfigurations.

As described above, the various indications of electrical dyssynchrony,such as statistical indexes, may be calculated for each of a pluralityof regions, e.g., posterior, left anterior, or the like, based ontorso-surface activations times from the region. Additionally,evaluating whether a patient is a candidate for CRT based on the atleast one indication of electrical dyssynchrony (806) may includedetermining the one or more indications of electrical dyssynchrony basedon torso-surface activation times both during intrinsic conduction ofthe heart, and during CRT. Differences between the indications duringintrinsic conduction and CRT may indicate that CRT would provide benefitfor the patient, e.g., that the patient is a candidate for CRT. Asdescribed above, the user may also evaluate whether a patient is acandidate for CRT based on at least one indication of electricaldyssynchrony based on intrinsic rhythm alone. Furthermore, monitoringthe at least one indication of electrical dyssynchrony (808) duringimplantation or a follow-up visit may include determining the one ormore indications of electrical dyssynchrony for each of a plurality oflead positions, electrode configurations, or other parameter valuesbased on torso-surface activation times resulting from delivery of CRTat the positions, or with the electrode configurations or parametervalues. In this manner, differences between dyssynchrony indicationsassociated with various locations, electrode configurations, orparameter values may be compared to determine preferred locations,configurations, or values.

Right ventricular (RV) pacing is less common than left ventricular (LV)pacing for resynchronization patients. RV only pacing may causearrhythmogenic effects in patients. Additionally RV failure is lesscommon in patients than LV failure. However, patients with right heartconduction delays, such as right bundle blockage, may benefit from RVonly pacing. Before administering RV only pacing, a patient's uniquesituation should be analyzed. Analyzing the function of the rightventricle may be difficult using traditional QRS techniques. Because theleft ventricle is larger, the electrical signals from the depolarizationof the left ventricle may obscure signals from the depolarization of theright ventricle.

FIG. 12 presents a method of determining if a patient is a goodcandidate for right ventricular only pacing according to someembodiments of the present invention. Referring now to FIG. 12, themethod beings by sensing the activation of atria in the patient. Thetiming of the activation is recorded as As 1202. Next, the rightventricle contraction time, RVs 1204, and the left ventricle contractiontime, LVs 1206, are recorded. RVs 1204 and LVs 1206 contraction timesmay be directly or indirectly measured. Further As 1202, RVs 1204, andLVs 1206 may be determined using the timing of paced beats or intrinsicbeats.

As 1202, RVs 1204, and LVs 1206, may be used to determine a patient'ssuitability for right ventricular only cardiac pacing. A patient may bea suitable candidate right ventricular only cardiac pacing therapy ifthe delay between As 1202 and RVs 1204 is greater than the delay betweenAs 1202 and LVs 1206. If the delay from As 1202 to RVs 1204 is less thanthe delay from As 1202 to LVs 1204 (see e.g., FIG. 12 step 1208), thepatient may not be a suitable candidate for right ventricular onlycardiac pacing and the standard of care CRT should be performed 1210.Additionally right ventricular only cardiac pacing may not be suitableif the intrinsic As to LVs time is not less than a predeterminedthreshold 1212. The predetermined threshold may include, but is notlimited to, 180 ms, 200 ms, 220 ms, or any other delay deemedappropriate for the patient.

Once a patient is identified as a candidate for right ventricular onlycardiac pacing, a proper pacing time should be determined. In someembodiments of the present invention, the right ventricular only cardiacpacing occurs a determined amount of time after a sensed or paced atrialevent. The atrioventricular delay time for right ventricular only pacingmay be fixed or calculated. In some embodiments of the presentinvention, the atrioventricular delay for right ventricular only pacingoccurs a fixed time after the sensed or paced atrial event determined asa percentage of the time between As 1202 and LVs 1206.

The optimal percentage of the time between As 1202 and LVs 1206 may bedetermined by evaluating the dyssynchrony and heterogeneity in the heartacross a range of percentage delays. The time interval between atrialsensed or paced event and the left ventricular sensed event may bedivided into several percentiles and the dyssynchrony and heterogeneityin the heart may be measured using multi-electrode ECG and methodsdisclosed above, during pacing the right ventricle only atatrioventricular delays equal to each of these percentile times.

According to some embodiments of the method, the optimal percentage forthe right ventricular paced delay may be determined after firstdetermining a patient's As 1202 and LVs 1206 (see, e.g. FIG. 12). Once apatient's As 1202 and LVs 1206 are recorded, a first percentage 1304 maybe selected. For example, the percentage may be, but is not limited to10% 15%, or 20%, 25%, 30%, 35%, 40%, 45%, 50%. The first percentage 1304of the time delay between As 1202 and LVs 1206 is used to pace thepatient's heart after a sensed atrial event (step 1308 in FIG. 13). Thatis, after a sensed atrial event, the patient's right ventricle is paceda period of time after the atrial event equal to a first percentage 1308of the time delay between As 1202 and LVs 1206. For example, if the As1202 to LVs 1206 delay is 180 ms, and the selected first percentage 1308is 50%, the patient's right ventricle is paced 90 ms after the atrialevent is sensed.

After the heart is paced with a specified right ventricle onlypercentage delay 1308, the global electrical heterogeneity of the heartand the resynchronization of the heart are determined using varioussystems or methods. The global electrical heterogeneity of the heart andthe resynchronization of the heart may be shown on a map where thevalues may be plotted in a spatial dimension corresponding to the torsoelectric signals received by electrodes placed on the body of thepatient. For example, FIG. 16 presents images showing electricalheterogeneity determined from the torso-electric signals received by theelectrodes on a patent's torso. Each data point corresponds to theheterogeneity of the signal received by each electrode as compared withthe set of received signals.

After the global electrical heterogeneity of the heart and theresynchronization of the heart are determined at a first percentage (50%in the example above), as second percentage is selected and the processis repeated. For example, a 60% RV-only delay may be selected as thesecond percentage. After the second percentage is selected, RV-onlypacing is again used with the second percentage used as to determine thetiming delay. After the RV-only pace is applied, the effects on theheart are again measured. Both the global electrical heterogeneity ofthe heart and the resynchronization of the heart are determined when theheart is paced with the second percentage.

This process may be repeated with various delay percentages. After eachdelay percentage is evaluated, the optimal delay percentage for thepatient may be selected. The selected delay may be the delay thatcorresponds to the lowest global electrical heterogeneity of the heartand the resynchronization of the heart should be selected as thispercentage reduces the overall stress on the heart and reduces thechanges of heart failure or even death. The same process may be repeatedduring atrial pacing (instead of atrial sensing) and the optimalpercentage (of atrial paced to LV sense) delay for delivering rightventricular only pacing following an atrial paced event may bedetermined. Additionally, other therapy parameters may be adjusted andthe corresponding heterogeneity and resynchronization of the heart maybe determined. As with optimizing right ventricular only pacing delaytimes, other therapy parameter conditions, such as the energy deliveredor the pacing vector may be varied. For example, in one embodiment adevice for pacing the patient's heart may adapt the right ventricularpacing time delay to account for changes in the intrinsic rhythm of theheart. FIG. 14 presents one embodiment of the present invention wherethe intrinsic As 1202 and intrinsic LVs 1206 is measured 1402 and thepercent corrected right ventricular delay applied 1404 to pace the rightventricle is determined using the intrinsic As 1202 and intrinsic LVs1206. After a threshold time 1406, for example one minute, the intrinsicAs 1202 and intrinsic LVs 1206 are measured again withholding rightventricular pacing for one, two or three beats, and the updated timebetween the As 1202 and the LVs 1206 is used to determine the newatrioventricular delay for subsequent right ventricular only pacing bymultiplying the optimal percentage with the updated delay between As andLVs.

FIG. 9 is a series of isochrones maps of cardiac activation times. Views900, 902 and 904 were constructed using torso-surface potentialsmeasured on the surface of the torso of a patient and projected ontothree dimensional models of the torso and the heart of the patient.Views 910, 912, and 914 were constructed using the measuredtorso-surface potentials of the same patient projected onto a differentmodel torso and model heart.

The three-dimensional representation of the hearts depicted in views900, 902, 904, 910, 912 and 914 were constructed using computertomography (CT) images of hearts obtained from databases of previouslyacquired cardiothoracic images. The locations of the electrodes, e.g.,electrodes 404 of sensing device 400B (FIG. 4B), on the torso of thepatient may be plotted to approximate locations on a model torso. Acomputer may be used to solve the inverse problem ofelectrocardiography, which includes determining the electrical activityon the surface of the heart that would produce the measuredtorso-surface potentials. The isochrones maps illustrated in views 900,902, 904, 910, 912 and 914 are based on images of hearts of twodifferent patients, which are also used to determine the geometry of theheart and relationship to the corresponding torso for solving theinverse problem of electrocardiography.

The model torsos and hearts may be constructed by manual orsemi-automatic image segmentation from available databases of previouslyacquired medical images (CT/MRI) of cardiomyopathy patients usingcommercially available software. Each model may be discretized usingboundary element method and may be further manipulated to account forpatients with different physical characteristics (e.g., large frame,medium frame and small frame) and heart sizes (e.g., x-large, large,medium, small).

A user may select the appropriate model torso and heart to suit thepatient, e.g., a patient having a large torso may be simulated with alarge frame model torso. In some examples, medical images of thepatient, e.g., CT or MRI images, may be manually or semi-automaticallysegmented, registered, and compared to a variety of available models forselection from amongst the models. One or more views of 2-D medicalimages (e.g., X-ray or fluoroscopy) may also be used. The user mayproject the measured torso-surface potentials from the torso of thepatient onto the corresponding locations on the model torso. The inverseproblem of propagating the electrical signals from the model torso tothe model heart may then be solved, and activation times for the modelheart may be estimated.

In one example in which the techniques of this disclosure were applied,human thoracic CT images for other subjects were obtained from imagedatabases. Semi-automatic image segmentation was performed on the imagesto generate the three-dimensional representation of the different modelsof hearts and torsos. In some examples, image segmentation may be donewith the AMIRA software package commercially-available from VisageImaging, Inc., of San Diego, Calif.

For the example, the electrode locations on the model torso wereapproximate. In particular, the locations electrodes on the patienttorso to the model torso the locations of the electrodes on the patienttorso were projected onto the surface of the model torso based on theorder in which the electrodes were mounted on the patient. For thepurpose of this projection, the patient and model torsos were dividedinto right anterior, left anterior, right posterior and left posteriorregions, using the sternum (anterior) and the spine (posterior) asreferences. Electrodes were arranged in vertical strips and three stripswere applied to each region of the torso. Electrodes in these regionswere projected on to the corresponding segments of the model torso. Themethod described is one of many techniques that may be used toregistered or map the geometrical distribution of measured electricalpotentials. For example, the measured electrical potentials may beinterpolated and resampled at electrode positions given by the model.Projection of the electrode locations from segments of the patient torsoonto the corresponding segments of the model torso in the correct orderenabled the activation patterns and spatial dispersion of activation onthe model heart to reflect the activation patterns and spatialdispersion of activation on the actual patient heart with relativeaccuracy. In one example, the inverse problem of electrocardiography maybe solved using the Matlab regularization toolbox (Hansen P C,Regularization Tools: A Matlab package for analysis and solution ofdiscrete ill-posed problems, Numerical Algorithms, 6 (1994), pp 1-35).

Input data-sets for solving the inverse problem consistent with theexample may include multi-electrode surface ECG measurements, the 3-DCartesian coordinates of the model heart and torso surfaces, and themesh over each model surface which specified the connectivity of thedifferent points on each surface. An output consistent with thetechniques of this disclosure may include activation times on the 3-Dmodel heart surface which can be visualized using visualization softwareand computer graphics tools. In some examples, the 3-D model heartsurface may be visualized using the tools in Matlab (Mathworks Inc,Natick, Mass.) or more advanced visualization software, such as Tecplot(Tecplot Inc, Bellevue, Wash.).

Comparing estimated cardiac activation times on two different, bothcardiac activation times determined from the same torso-surfacepotential signals for one subject, show similar patterns anddistribution. For example, region 906 of views 902 and 904 correspondsin size and activation time to region 916 of views 912 and 914. Region908 of views 902 and 904 corresponds to region 918 of views 912 and 914.Additionally, the standard deviations of activations time for bothmodels are both derived from the same torso-surface potentials for onesubject, were similar (17.6 and 15.5 ms). The overall pattern of cardiacactivation and measures of dispersion of cardiac activation times arethus not dependent on a specific heart-torso model. Using a genericheart-torso model may allow a user to create an isochrones model of thecardiac activation time suitable for diagnosis and observation whileavoiding expense, inconvenience, and radiation exposure that may becaused by the CT scan or other imaging that may be used to produce apatient-specific model of the heart of the patient.

FIG. 10 is a flow diagram illustrating an example operation of a systemto measure the cardiac electrical dyssynchrony of a patient via thecardiac activation times. Processing unit 500 determines the location ofthe electrodes 404, e.g., based on an analysis of imaging data by anelectrode location registration module 524. Processing unit projects thelocations of the electrodes onto a model torso, e.g., a selected modeltorso (1002).

A cardiac event, e.g., depolarization, occurs causing an electricalsignal to propagate through the torso of the patient, and register onthe electrodes distributed on the surface of the torso of the patient.The torso-surface potential signals sensed by the electrodes may bereceived by processing unit 500 (1004). The processing unit may projectthe signals onto the surface of the model torso based on the determinedlocations of the electrodes (1006).

The processing unit may solve the inverse problem of determiningepicardial potentials based on torso-surface potentials (1008). Theprocessing unit may then calculate cardiac activation times at a varietyof locations of the model heart based upon the projected torso-surfacepotentials (1010). The cardiac activation times may be computed by, forexample, determining the greatest negative slope of the epicardialelectrogram potentials (1016) or by least squares minimization in thesolution of the inverse problem (1018). The cardiac activation time maybe displayed (1012). Examples of potential methods for displayingcardiac activation times include isochrone maps (1014) and a moviedepicting the progression of the wavefront over the model heart (1016).The processing unit may be configured to allow a user select between, ordisplay simultaneously, various display modes, including the wave frontmovie and isochrones maps. Additionally, one or more indices of cardiacelectrical dyssynchrony may be calculated (1018), including the SDAT(1020), RAT (1022), and PLAT (1024).

For solving the inverse problem (1008), epicardial potentials may becomputed from projected torso-surface potentials assuming a source-lessvolume conductor between the heart and the torso in an inverse Cauchyproblem for Laplace's equation. Alternatively, an analytic relationbetween torso-surface potentials and the cardiac transmembrane potentialmay be assumed. Additionally, cardiac activation times may be estimated(1010) from the steepest negative slope of the epicardial electrogramsdetermined from the inverse solution of the torso-surfacepotential/epicardial potential transformation. In other examples, modeltorso-surface potentials may be simulated based on the analyticrelationship approach to determining the cardiac transmembrane potentialfrom torso-surface potential. Cardiac activation times (parameters inthe analytic relationship) may be computed based on minimizing the leastsquare difference between the projected model torso-surface potentialsand simulated torso-surface potentials.

In some examples, the construction of a torso-surface activation timesisochrone map (1014), wavefront animation (1016), or other graphicalrepresentation of cardiac electrical dyssynchrony, as well as thecalculation of indices of cardiac electrical dyssynchrony (1018), may beperformed for a particular region of the model heart based the computedcardiac activation times in such regions. Graphical representations andindices of cardiac electrical dyssynchrony may be determined for each ofa plurality of regions based on the computed cardiac activation times insuch regions. In some examples, the representations and indices forvarious regions may be presented together or compared.

FIG. 11 is a flow diagram illustrating an example technique formeasuring the cardiac electrical dyssynchrony of a patient viadetermined cardiac activation times. The techniques may comprisedetermining the location of a plurality of electrodes (1100), projectingthe location of the electrodes onto the surface of a model torso (1102),recording the output of the plurality of electrodes (1104), projectingthe output of the plurality of the electrodes on the surface of themodel torso (1106), solving the inverse problem (1108) and determiningthe cardiac activation times for a model heart from the projectedtorso-surface potentials (1110). The cardiac activation times may bedisplayed (1112). One or more indices of electrical dyssynchrony may becalculated (1114). The output, the indices of cardiac electricaldyssynchrony and cardiac activation time maps, may be monitored,allowing a user to diagnose the patient, adjust the position of CRTelectrodes during implantation (1118), or adjust A-V or V-V pacingintervals of the CRT device (1120).

A user may monitor the output of the calculations (1116), e.g., the atleast one indices of cardiac electrical dyssynchrony or the display ofcardiac activation times. Monitoring these values may allow the user todiagnose a condition that might benefit from CRT or to evaluate theeffectiveness of CRT. For example, the at least one index of cardiacelectrical dyssynchrony may indicate the presence of damage toelectrical conductivity of the heart of the patient, for example thepresence of a left or right bundle branch block, that may not beapparent from the examination of a standard 12 lead ECG readout. A largeSDAT indicates that the activation of the ventricles is occurring over alarge time span, indicating that the depolarization of the ventricles isnot occurring simultaneously. A large RAT also indicates a broad rangeof activation times and asynchronous contraction of the ventricles. Ahigh PLAT may indicate that a specific region of the heart, e.g., theposterior regions more associated with the left ventricle, is failing toactivate in concert with the measured QRS complex.

The user may adjust the positioning of CRT electrodes, e.g., electrodes108, 110, and 112 of IMD 100 (FIG. 1) according to the displayed cardiacactivation times or the indices of cardiac electrical dyssynchrony. Forexample, the processing unit, via a display, may implement systems thatdisplays shifting colors based on the percentage change of the indicesof cardiac electrical dyssynchrony. As the position of the CRTelectrodes are adjusted (1118), the displayed colors may shift from redto yellow to green based on the percentage improvement of the indices ofcardiac electrical dyssynchrony. This may allow a user to rapidlydetermine if the adjustments of the CRT electrodes are having a positiveeffect on the symptoms of the patient. In another example, the user mayadjust the A-V or V-V pacing intervals of an implanted CRT device (118).The minimum value of the indices of cardiac electrical dyssynchrony mayindicate adequate pacing intervals. Isochrone maps or wave frontpropagation movies may also be used to aid in CRT adjustments or todiagnose conditions that may be responsive to CRT treatment.

Further, the extent of applied cardiac stimulation after the heart ispaced may be determined by comparing the number of electrodes thatactivate before a predetermined time from the onset of the activationprocess. This comparison can be utilized to estimate the extent ofcardiac tissue capture from the pacing event. The amount of capture inlocalized areas of the heart may be determined if the location of theelectrodes is correlated to specific parts of the heart. For example,FIG. 15 presents a flow diagram detailing a method according to oneembodiment of the invention for determining the extent of cardiac tissuestimulation. The method begins when torso-potential signals are receivedby electrodes 1502 on the patent. The approximate onset of ventriculardepolarization may be identified by the earliest onset of QRS complex onany torso-lead. Similarly the approximate offset may be determined bythe latest offset of QRS complex on any torso-lead.

Activation times are determined at each electrode within the detectedonset and offset of a QRS complex. The number of electrodes withactivation times earlier than a predetermined time threshold from theonset of the corresponding depolarization (QRS) complex is determined.In another embodiment the number of electrodes with activation timesearlier than a predetermined time-threshold from the earliest detectedactivation-time may be determined. The threshold may be 5 ms, 10 ms, 15ms, 20 ms. For example, the threshold may exclude signals that arereceived by the electrodes more than 20 ms after a paced or intrinsicbeat. The number of activated electrodes activating earlier than thepre-determined threshold is then compared to the total number ofelectrodes 1506 to determine the extent of applied cardiac tissuestimulation 1508. The extent of applied cardiac tissue stimulation maybe determined using a paced or an intrinsic beat of the heart. If a pacebeat is used, care should be taken to avoid interference with theintrinsic beat of the heart. In some embodiments, avoiding interferencewith the intrinsic beat of the heart may take the form of pacing theheart with a very short atrioventricular interval (less than 50 ms)thereby electrically activating the entire heart by pacing without anycontribution of the intrinsic electrical conduction of the heart. In theabsence of regular one-to-one atrioventricular conduction, interferencewith the intrinsic beat may be avoided by pacing the heart rapidly.Determining the extent of tissue capture may be performed by applyingdifferent magnitudes of the predetermined threshold, for example, 10 msand 20 ms. Different extents of tissue capture may be determined for theinterval between the two time-thresholds, indicating the speed at whichelectrical activations spreads. For example if 5% of electrodes activateearlier than 10 ms and 20% activate earlier than 20 ms, the differentialextent of capture during the interval from 10 ms to 20 ms from onset ofdepolarization will be 15%. This information may be helpful as speed ofpropagation of electrical activation may vary with time during thedepolarization cycle. In one embodiment, the speeds of cardiacconduction may be determined applying different timing thresholdsthroughout the entire QRS complex to determine an average rate of changeof propagation speed over the depolarization cycle.

As indicated above, to facilitate evaluating the whether a patient is acandidate for CRT based on the monitored output (1116), the one or moreindications of cardiac electrical dyssynchrony, e.g., indices orgraphical indications, may be determined based on torso-surfaceactivation times during both intrinsic conduction of the heart, andduring CRT. Differences between the indications during intrinsicconduction and CRT may indicate that CRT would provide benefit for thepatient, e.g., that the patient is a candidate for CRT. Furthermore,during implantation or a follow-up visit, the one or more indications ofcardiac electrical dyssynchrony may be determined for each of aplurality of lead positions, electrode configurations, or otherparameter values based on torso-surface activation times resulting fromdelivery of CRT at the positions, or with the electrode configurationsor parameter values. In this manner, differences between cardiacelectrical dyssynchrony indications associated with various locations,electrode configurations, or parameter values may be compared todetermine preferred locations, configurations, or values.

Various examples of this disclosure have been described. However, one ofordinary skill in the art will appreciate that various modifications maybe made to the described embodiments without departing from the scope ofthe claims. For example, although SDAT, RAT and PLAT have been discussedas example statistical indices of the dispersion of activation times,other indices or metrics of the dispersion of the timing ofdepolarization may be determined according the techniques of thisdisclosure. As one example, a range of activation times between twospecific regions, e.g., anterior and posterior, may be determined. Asanother example, a range or variability of activation times afterexcluding certain locations or regions may be determined according tothe techniques of this disclosure. The excluded locations or regions maybe those that are believed to be scar tissue, e.g., identified by lowamplitude electrical signals, or locations or regions that are beyondthe extent of the far-field QRS complex. In general, calculation of anindex may include determining any statistical or other value based onthe torso-surface or cardiac activation times, or some subset thereof.These and other examples are within the scope of the following claims.

The present invention has been described above with the aid offunctional building blocks illustrating the implementation of specifiedfunctions and relationships thereof. The boundaries of these functionalbuilding blocks have been arbitrarily defined herein for the convenienceof the description. Alternate boundaries can be defined so long as thespecified functions and relationships thereof are appropriatelyperformed.

The foregoing description of the specific embodiments will so fullyreveal the general nature of the invention that others can, by applyingknowledge within the skill of the art, readily modify and/or adapt forvarious applications such specific embodiments, without undueexperimentation, without departing from the general concept of thepresent invention. Therefore, such adaptations and modifications areintended to be within the meaning and range of equivalents of thedisclosed embodiments, based on the teaching and guidance presentedherein. It is to be understood that the phraseology or terminologyherein is for the purpose of description and not of limitation, suchthat the terminology or phraseology of the present specification is tobe interpreted by the skilled artisan in light of the teachings andguidance.

The breadth and scope of the present invention should not be limited byany of the above-described exemplary embodiments, but should be definedonly in accordance with the following claims and their equivalents.

The claims in the instant application are different than those of theparent application or other related applications. The Applicanttherefore rescinds any disclaimer of claim scope made in the parentapplication or any predecessor application in relation to the instantapplication. The Examiner is therefore advised that any such previousdisclaimer and the cited references that it was made to avoid, may needto be revisited. Further, the Examiner is also reminded that anydisclaimer made in the instant application should not be read into oragainst the parent application.

What is claimed is:
 1. A method of determining the extent of applied cardiac tissue stimulation due to pacing comprising: applying electrodes on a patient's torso; pacing the patient's cardiac tissue; receiving torso-surface potential signals detected by the electrodes; determining an activation time for each electrode; determining the number of electrodes that register an activation time that meets predetermined criteria; calculating a percentage index by dividing the number of electrodes that registered an activation time that meets a predetermined criteria by the total number of electrodes distributed on the patient's torso; and determining the extent of applied cardiac tissue stimulation due to pacing based on the percentage index.
 2. The method of claim 1, wherein the pacing of the cardiac tissue is timed to avoid interference with the intrinsic rhythm of the heart.
 3. The method of claim 1, wherein the predetermined criteria comprises a predetermined activation time threshold.
 4. The method of claim 1, wherein the predetermined criteria comprises a predetermined time period within which the activation time of electrodes must be registered.
 5. The method of claim 4, wherein the predetermined time period is about 5 ms, 10 ms, 15 ms, or 20 milliseconds from a specified time origin where the specified time origin is the earliest activation time detected for a corresponding depolarization cycle.
 6. The method of claim 4 wherein the predetermined time period is a percentile of the activation-times registered by the electrodes.
 7. The method of claim 1, further comprising adjusting a therapeutic parameter value based on the extent of applied cardiac tissue electrical stimulation due to pacing.
 8. The method of claim 7, wherein the therapeutic parameter comprises the magnitude of the energy applied by the pacing source.
 9. The method of claim 7, wherein the therapeutic parameter comprises the direction of a pacing vector applied by the pacing source.
 10. The method of claim 9, wherein the direction of the pacing vector is determined from the geometry of the device.
 11. A system to determine the extent of applied cardiac tissue stimulation due to pacing, the system comprising: electrodes configured to be distributed on a patent's torso; a pacing device configured to stimulate the patent's cardiac tissue; a processing unit configured to: determine the number of electrodes that register an activation time that meet as predetermined criteria; calculate a percentage index by dividing the number of electrodes that registered activation times that meet the predetermined criteria by the total number of electrodes distributed on the patient's torso; and determine the extent of applied cardiac tissue stimulation due to pacing based on the percentage index.
 12. The system of claim 11, wherein the distributed electrodes comprise at least 20 electrodes.
 13. The system of claim 11, wherein the pacing device is implanted in the patient and comprises a lead in direct contact with cardiac tissue.
 14. The system of claim 13, wherein the pacing device comprises the processing unit.
 15. The system of claim
 13. wherein the pacing device comprise two electrodes located on the same lead.
 16. The system of claim 14, wherein the pacing device communicates wirelessly with the processing unit.
 17. The system of claim 11, wherein the pacing device comprises an external device for applying pacing using an ultrasound wave.
 18. A method of determining the extent of applied cardiac tissue stimulation due to pacing comprising: applying stimulation to the patient's cardiac tissue and receiving potential signals detected at a first time period; determining the extent of applied cardiac tissue stimulation due to pacing based on activation times derived from the potential signals received at the first time period; adjusting a therapeutic parameter related to the delivery of the stimulation to the patient's cardiac tissue based on the determined extent of applied cardiac tissue electrical stimulation due to pacing, in order to meet a predetermined treatment goal; applying stimulation to the patient's cardiac tissue and receiving potential signals detected at a second time period; determining the extent of applied cardiac tissue stimulation due to pacing based on the potential signals received at the second time period; determining if the adjustment of the therapeutic parameter resulted in meeting the predetermined treatment goal.
 19. The method of claim 18, wherein the therapeutic parameter is the magnitude of the energy applied by the pacing source.
 20. The method of claim 18, wherein the therapeutic parameter is the direction of a pacing vector applied by the pacing source.
 21. The method of claim 20, wherein the direction of the pacing vector is determined from the geometry of a pacing device.
 22. The method of claim 18, wherein the therapeutic parameter is a timing interval between successive stimulations of the cardiac tissue.
 23. The method of claim 18, wherein the predetermined treatment goal comprises increasing the extent of applied cardiac tissue stimulation due to pacing within a predetermined time period.
 24. The method of claim 18, wherein the predetermined treatment goal comprises decreasing the extent of applied cardiac tissue stimulation due to pacing within a predetermined time period.
 25. A system to determine the extent of applied cardiac tissue stimulation due to pacing, the system comprising: electrodes configured to be distributed on a patent's torso; means for stimulating the patent's cardiac tissue; means for determining the number of electrodes that register an activation time that meet as predetermined criteria; means for calculating a percentage index by dividing the number of electrodes that registered activation times that meet the predetermined criteria by the total number of electrodes distributed on the patient's torso; and means for determining the extent of applied cardiac tissue stimulation due to pacing based on the percentage index.
 26. The system of claim 25, wherein the means for stimulating the patent's cardiac tissue is implanted in the patient.
 27. The system of claim 25, wherein the means for stimulating the patent's cardiac tissue is external to the patient's body.
 28. The system of claim 25, wherein the means for determining the extent of applied cardiac tissue stimulation due to pacing is implanted in the patient.
 29. The system of claim 25, wherein the means for determining the extent of applied cardiac tissue stimulation due to pacing is external to the patient's body.
 30. A method of determining the extent of applied cardiac tissue stimulation due to pacing comprising: applying electrodes on a patient's torso; pacing the patient's cardiac tissue, the pacing of the cardiac tissue is timed to avoid interference with the intrinsic rhythm of the heart; receiving torso-surface potential signals detected by the electrodes; determining an activation time for each electrode; determining the number of electrodes that register an activation time that meets a predetermined criteria; calculating a percentage index by dividing the number of electrodes that registered an activation time that meets the predetermined criteria, the predetermined criteria comprises a predetermined time period within which the activation time of electrodes must be registered, by the total number of electrodes distributed on the patient's torso; and determining the extent of applied cardiac tissue stimulation due to pacing based on the percentage index. 